Severe Heart Failure With Reduced Ejection Fraction Research Articles

A matter of sex-persistent predictive value of MECKI score prognostic power in men and women with heart failure and reduced ejection fraction: a multicenter study.

A sex-based evaluation of prognosis in heart failure (HF) is lacking. We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women). S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

Guideline-directed medical therapy in severe heart failure with reduced ejection fraction: An analysis from the HELP-HF registry.

Persistent symptoms despite guideline-directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data on GDMT use, dose, and prognostic implications are lacking. We included 699 consecutive patients with HFrEF and at least one 'I NEED HELP' marker for advanced HF enrolled in a multicentre registry. Beta-blockers (BB) were administered to 574 (82%) patients, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, ≥50% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi/ARB/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA-ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.84, and HR 0.74, 95% CI 0.58-0.95, respectively). In a large, real-world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity.

The effect of long-term application of guideline-directed medical therapy on systolic blood pressure in hospitalized patients with heart failure with reduced ejection fraction

Abstract Background According to the current guidelines in heart failure (HF) with reduced ejection fraction (HFrEF) the implementation and titration of guideline-directed medical therapy (GDMT) is recommended. Although just symptomatic hypotension is known as a factor limiting the initiation or uptitration of GDMT, in everyday practice asymptomatic hypotension often has a negative impact on the long-term application of GDMT in HFrEF, even though patients with lower systolic blood pressure (SBP) have worse prognosis. Aim To assess the application of combined neurohormonal antagonist therapy (triple therapy [TT]: RASi[ACEi/ARB/ARNI]+βB+MRA) based on SBP during an index HF hospitalization, and to evaluate the long-term application of TT on SBP and on mortality. Patients and methods: The data of 247 consecutive HFrEF patients (male:75%, age:66[56-74]years, ischemic:46%, diabetes:40%, hypertension:63%, atrial fibrillation:46%, LVEF:25[20-30]%, eGFR:58[39-73]ml/min/1.73m2,SBP:118[102-134]mmHg) were analysed retrospectively, who had been admitted to the HF Unit of our tertiary centre due to HF in 2019-2021 and then were followed up for one year. Patients were divided into three SBP categories based on SBP measured at admission: SBP1:<100mmHg (n = 46), SBP2:100-120mmHg (n = 98), SBP3:>120mmHg (n = 103) (respectively). The applicability of TT at hospital discharge and at 1 year were assessed comparing SBP categories with Chi-square test. The changes of SBP within each category were compared with Wilcoxon test. 1-year all-cause mortality (ACM) was investigated with Kaplan-Meier method and log-rank test. Results At discharge, 77% of the patients received TT in the total cohort. Lower SBP at admission led to lower application ratio of βB (72-89-87%, p = 0.019), while RASi and MRA use was consistent across SBP categories (87-89-89%; 91-98-93%, p>0.05). TT application at discharge did not differ significantly among the subgroups (65-81-79%, p = 0.107). 1-year ACM was 23% in the total cohort, with significantly higher mortality rates in lower SBP groups (33-27-15%, p = 0.022). At 1 year TT application remained high; 65% in SBP1, 78% in SBP2 and 72% in SBP3 group. No differences (p>0.05) were seen in terms of βB (87-88-91%), RASi (81-89-84%) and MRA use (77-86-82%) in SBP groups. In the effect of GDMT, in the SBP1 and SBP2 group, SBP significantly (p<0.0001) rose (SBP1: from 92[85-95] to 110[95-127]mmHg, SBP2: from 111[104-117] to 124[110-133]mmHg; discharge vs. 1 year), while in the highest SBP group significant decrease was verified (from 137[129-146] to 130[118-145]mmHg, p = 0.002). Conclusions Our study results confirmed that low SBP is associated with a poor prognosis in HFrEF. Low SBP is a relevant influencing factor of GDMT initiation and long-term application, even though among these patients increase in SBP can be expected due to the use of GDMT. Our results indicate that low SBP should not make physicians be hesitant to optimize therapy in severe HFrEF.

Long-term clinical course and prognostic factors of heart failure with reduced ejection fraction (HFrEF) patients underwent primary prophylactic implantable cardioverter defibrillator (ICD)

Abstract Background For decades, ICD is a well-established therapy for improving prognosis of structural heart disease with severe cardiac dysfunction, and ICD for primary prophylaxis against sudden cardiac death were routinely provided. However, long-term prognosis and clinical course are different in each individual patient with an ICD, and it is moreover unclear what kind of factors might have influences on their clinical outcomes. Purpose The aim of this study is to clarify long-term prognosis and predictors of future major adverse cardiac events (MACEs) in HFrEF patients with an ICD as primary prophylaxis in Japanese population. Methods We retrospectively analyzed our ICD database. Patients underwent primary prophylactic ICD implantation from 2006 to 2020 at our institute and met the criteria of ICD recommendation of the latest Japanese guideline. Its requirements are receiving optimal medication therapy, symptomatic heart failure (New York Heart Association classification II or greater), and severe cardiac dysfunction (left ventricular ejection fraction (LVEF) is 35% or less). Additionally, prior NSVT is considered Class I ICD recommendation. In the case of ischemic cardiomyopathy (ICM), ICD implantation was done at least 40 days after myocardial infarction and at least 90 days after revascularization. MACEs were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. Results A total of 148 consecutive patients were enrolled (male, 120 (81%); age, 62.1±11.8 years; LVEF, 23.0±5.86%; left ventricular end-diastolic diameter (LVDd), 67.6±9.26mm; paroxysmal or persistent atrial fibrillation (AF), 38 (26%); NSVT, 113 (76%); use of class III antiarrhythmic drugs, 48 (32%); ICM, 49 (33%); cardiac resynchronization therapy (CRT), 63 (43%)). One hundred twenty patients (81%) were programmed with a shock-only zone over 200 beats per minute. The median follow-up duration was 58.5 months. Among those 148 patients, MACEs were occurred to 60 patients (41%). As a result of dividing all patients into two groups by the occurrence of MACE, LVEF and LVDd were worse in MACE(+) group, whereas, MACE(−) had greater number of co morbidities. The results of cox-regression analysis showed LVDd (HR: 1.07, 95% CI: 1.03–1.12, p<0.001), AF (HR: 2.88, 95% CI: 1.56–5.31, p<0.001) and ICM (HR: 1.78, 95% CI: 1.00–3.16, p=0.049) were the independent predictors of MACEs (Table). However, initial ICD programming was not related to the occurrence of MACE. Conclusions The incidence of MACEs in patients with an ICD and severe HFrEF was substantially high in this Japanese population. Etiology of ICM, left ventricle size, and AF were the potential risk factors for future MACEs. Funding Acknowledgement Type of funding sources: None.

Liver tests and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF.

Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium-glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment. We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37-2.17], p < 0.001; and 1.52 [1.12-2.07], p=0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests. Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests. ClinicalTrials.gov NCT03036124.

Negative prognostic implications of non-sustained ventricular tachycardias in patients after prophylactic defibrillator implantation

Abstract Funding Acknowledgements Type of funding sources: None. Background Non-sustained ventricular tachycardia (NSVT) is frequent phenomenon in severe heart failure with reduced ejection fraction (HFrEF) patients, and causes any negative impacts on such patients. In the Japanese Circulation Society (JCS) and Japanese Heart Rhythm Society (JHRS) guidelines, NSVT is regarded as a major component of indication for implantable cardioverter defibrillator (ICD) implantation. However, the long-term prognostic significance of NSVT in severe HFrEF is incompletely resolved. Purpose The aim of this study is to investigate the relation between prior NSVT episodes and major adverse cardiac events (MACEs) in HFrEF patients with an ICD as primary prophylaxis. Methods We retrospectively analyzed our ICD database. Patients underwent primary prophylactic ICD implantation from 2007 to 2018 following ICD recommendation of JCS and JHRS guidelines. Patients met the criteria of receiving optimal medication therapy, symptomatic heart failure (New York Heart Association classification II or greater), and severe cardiac dysfunction (left ventricular ejection fraction (LVEF) is 35% or less). In the case of ischemic cardiomyopathy (ICM), implantation of ICD was done at least 40 days after myocardial infarction and at least 90 days after revascularization. Incidence of NSVT episodes were identified through daily electrocardiogram (ECG), Holter ECG or monitor ECG in the hospital. MACEs were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. Results A total of 148 consecutive patients were enrolled (male, 120 (81%); age, 62.1±11.8 years; LVEF, 23.0±5.86%; left ventricular end-diastolic diameter (LVDd), 67.6±9.26mm; paroxysmal or persistent atrial fibrillation (AF), 38 (26%); NSVT, 113 (76%); use of class III antiarrhythmic drugs, 48 (32%); ICM, 49 (33%); cardiac resynchronization therapy (CRT), 63 (43%)). The median follow-up duration was 58.5 months. As a result of comparison of the Kaplan-Meier curve between NSVT group (n=113) and non-NSVT group (n=35), cardiovascular death, heart failure hospitalization, and appropriate ICD therapy were not statistically different (Figures). Of those, MACEs were occurred to 60 patients (41%). The results of cox-regression analysis showed LVDd (HR: 1.07, 95% CI: 1.03-1.12, p&amp;lt;0.001), AF (HR: 2.88, 95% CI: 1.56-5.31, p&amp;lt;0.001) and ICM (HR: 1.78, 95% CI: 1.00-3.16, p=0.049) were the independent predictors of MACEs, however NSVT was not (Table). Conclusions In this Japanese population, the long-term prognosis of severe HFrEF patients is considered to be comparable regardless of prior NSVT episodes. However, the incidence of MACEs in patients with severe HFrEF after ICD implantation was substantially high. ICM, left ventricle size, and atrial fibrillation were the potential risk factors for MACEs as the previous reports showed.

PO-688-03 PROGNOSTIC IMPLICATIONS OF NON-SUSTAINED VENTRICULAR TACHYCARDIAS IN SEVERE HEART FAILURE PATIENTS AFTER PROPHYLACTIC DEFIBRILLATOR IMPLANTATION

Non-sustained ventricular tachycardia (NSVT) causes any negative impacts on severe heart failure with reduced ejection fraction (HFrEF) patients. Thus, the prognostic significance of NSVT in severe HFrEF is incompletely resolved after implantable cardioverter defibrillator (ICD) implantation.

Unmasking Pulsus Alternans In Patients With Heart Failure With Reduced Ejection Fraction. The Importance Of Upright Exercise

<h3>Background</h3> : Pulsus alternans (PA), typically observed in a supine resting position, is a poor prognostic indicator among patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that PA may not be present in the supine position, but only when upright. <h3>Methods</h3> : 27 patients with severe HFrEF completed invasive cardiopulmonary exercise testing (CPET) with Swan-Ganz and radial arterial catheters. Hemodynamics were recorded in supine and upright resting positions. During exercise on upright cycle ergometry, hemodynamics were collected at two submaximal levels of exercise below ventilatory threshold (Steady-States 1 and 2) and peak effort. Breath-by-breath gas-exchange parameters were measured by indirect calorimetry. <h3>Results</h3> : Baseline characteristics are displayed in <b>Table 1</b>. Twenty-one participants showed no evidence of PA in either supine or upright position. However, six participants were found to have PA when in an upright resting but not supine resting position (<b>Figure 1</b>). Exercise hemodynamics and gas exchange parameters are displayed in <b>Table 2</b>. Maximal oxygen uptake (VO₂Max) was severely reduced, the cardiac output response to exercise was blunted, and exertional cardiac filling pressures were abnormal in both groups. <h3>Conclusions</h3> : PA, a poor prognostic indicator, may manifest in an upright but not supine position among patients with HFrEF. As human beings are upright and bipedal, this novel finding reinforces the importance of upright exertional hemodynamic assessments to guide risk-stratification and management.

Abstract 11183: A Classificatory Analysis of Right Heart Geometry and Dysfunction Provides Prognostic Stratification in Heart Failure of Any Left Ventricular Ejection

Introduction: The prognostic role of the left heart dysfunction is established in heart failure (HF). However, focusing only on left ventricular ejection fraction (LVEF) may be reductive as HF with preserved ejection fraction (HFpEF) yields to poor outcomes, similarly to HF with reduced ejection fraction (HFrEF). Hypothesis: We investigated the prognostic role of the right ventricle (RV) phenotype through a classification based on RV end diastolic diameter (RVEDD) and tricuspid annulus systolic excursion (TAPSE) in chronic HF of any LVEF. Methods: We retrospectively examined two well-defined population of ambulatory patients with chronic HF: severe HFrEF (LVEF≦35%) and HFpEF (LVEF≧55%), all receiving optimal guideline-directed medical and device therapy, followed at a dedicated outpatient HF clinic. Patients were categorized by echocardiography based on RVEDD (cut-off 42 mm) and TAPSE (cut-off 17 mm) into four groups (above and below cut-offs): not dilated and not hypokinetic (NDNH), dilated and not hypokinetic (DNH), not dilated and hypokinetic (NDH) and dilated and hypokinetic (DH). Results: Among 256 patients (mean age 67±12 years, 75% men, 75% HFrEF, 60% ischemic), RVEDD and TAPSE were available for 202. Distribution of NDNH, NDH, DNH and DH is reported in the figure. Over a median follow-up of 4 years, 62 deaths occurred; KM-survival curves are shown in figure. After multivariable adjustment for age, HFpEF/HFrEF, and ischemic etiology, patients with DNH and DH showed increased risk of mortality (HR 2.4 95%CI 1.1-5.1 p=0.024; and 3.4 95%CI 1.7-6.7 p&lt;0.001 respectively) compared to NDNH, with NDH showing comparable risk (HR 1.6 95%CI 0.9-3.7 p=0.232). Conclusions: In chronic HF receiving optimal medical and device therapy, a simple and easy to use RV classificatory analysis is worth of consideration out of LVEF categorization. RV dimensions rather than motility drive the mortality rate independently of age, HFpEF/HFrEF phenotype and HF etiology.

Phenotyping the right heart according to left ventricular geometry patterns in severe HFrEF

Abstract Background Right ventricular (RV) failure significantly impact on heart failure with reduced ejection fraction (HFrEF) prognosis. How and whether specific functional and geometrical phenotypes of the RV function adapt and combined with left ventricular (LV) geometry is unknown. Purpose To test the RV function across LV geometrical patterns looking at respective prognostic roles. Methods We retrospectively examined a population of patients homogenously diagnosed with chronic HFrEF (defined as LV ejection fraction (EF) less than 35%) and treated with optimal therapy (OT) and all implanted with ICD for primary prevention of sudden cardiac death. Patients were categorized by echocardiography according to remodeling pattern based on left ventricular mass index and relative wall thickness into four groups: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH) and eccentric hypertrophy (EH). RV parameters were: tricuspid annulus plane systolic excursion (TAPSE), TAPSE/pulmonary artery pressures (PAPs), RV basal diameter and fractional area change (FAC). Outcome variable was all-cause mortality, assessed with multivariable Cox proportional hazard (PH) models. Results Among 193 patients (age 66±11 years, 81% men, 74% with ischemic etiology of HF and EF 28±5%) 21% had NG, 3% had CR, 8% had CH, and 68% had EH. Distribution of RV echo parameters across LV remodeling groups is shown in table 1. Over a median follow-up time of 4 (1.9 – 6.1) years, 65 deaths occurred. In multivariable Cox PH models adjusted for age, LVEF, ischemic etiology and LV geometry, TAPSE, TAPSE/PAPs, RV basal diameter and FAC strongly and independently predicted the outcome variable [HR 0.92 (95% C.I. 0.86–0.98), HR 0.08 (95% C.I. 0.01–0.57), HR 1.87 (95% C.I. 1.29–2.71), HR 0.97 (95% C.I. 0.95–1.00), respectively all p-value &amp;lt;0.05]. Conclusion In a homogeneously defined population of severe HFrEF outpatients receiving OT, the majority showed EH remodeling pattern, which did not predict the primary outcome. LV geometry did not further stratify patients in this high risk group. Conversely, RV dysfunction proved to be a strong predictor of mortality, independently of age, LV function and etiology of HF, regardless LV morphology. Funding Acknowledgement Type of funding sources: None.

Treatable cardiac disease in hospitalised COPD exacerbations.

IntroductionAcute exacerbations of COPD (AECOPD) are accompanied by escalations in cardiac risk superimposed upon elevated baseline risk. Appropriate treatment for coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF) could improve outcomes. However, securing these diagnoses during AECOPD is difficult, so their true prevalence remains unknown, as does the magnitude of this treatment opportunity. We aimed to determine the prevalence of severe CAD and severe HFrEF during hospitalised AECOPD using dynamic computed tomography (CT).MethodsA cross-sectional study of 148 patients with hospitalised AECOPD was conducted. Dynamic CT was used to identify severe CAD (Agatston score ≥400) and HFrEF (left ventricular ejection fraction ≤40% and/or right ventricular ejection fraction ≤35%).ResultsSevere CAD was detected in 51 of 148 patients (35%), left ventricular systolic dysfunction was identified in 12 cases (8%) and right ventricular systolic dysfunction was present in 18 (12%). Clinical history and examination did not identify severe CAD in approximately one-third of cases and missed HFrEF in two-thirds of cases. Elevated troponin and brain natriuretic peptide did not differentiate subjects with severe CAD from nonsevere CAD, nor distinguish HFrEF from normal ejection fraction. Undertreatment was common. Of those with severe CAD, only 39% were prescribed an antiplatelet agent, and 53% received a statin. Of individuals with HFrEF, 50% or less received angiotensin blockers, beta blockers or antimineralocorticoids.ConclusionDynamic CT detects clinically covert CAD and HFrEF during AECOPD, identifying opportunities to improve outcomes via well-established cardiac treatments.

Estimating the Lifetime Benefits of Treatments for Heart Failure

ObjectivesThis study compared ways of describing treatment effects. The objective was to better explain to clinicians and patients what they might expect from a given treatment, not only in terms of relative and absolute risk reduction, but also in projections of long-term survival. BackgroundThe restricted mean survival time (RMST) can be used to estimate of long-term survival, providing a complementary approach to more conventional metrics (e.g., absolute and relative risk), which may suggest greater benefits of therapy in high-risk patients compared with low-risk patients. MethodsRelative and absolute risk, as well as the RMST, were calculated in heart failure with reduced ejection fraction (HFrEF) trials. ResultsAs examples, in the RALES trial (more severe HFrEF), the treatment effect metrics for spironolactone versus placebo on heart failure hospitalization and/or cardiovascular death were a hazard ratio (HR) of 0.67 (95% confidence interval [CI]: 0.5 to 0.77), number needed to treat = 9 (7 to 14), and age extension of event-free survival +1.1 years (−0.1 to + 2.3 years). The corresponding metrics for EMPHASIS-HF (eplerenone vs. placebo in less severe HFrEF) were 0.64 (0.54 to 0.75), 14 (1 to 22), and +2.9 (1.2 to 4.5). In patients in PARADIGM-HF aged younger than 65 years, the metrics for sacubitril/valsartan versus enalapril were 0.77 (95% CI: 0.68 to 0.88), 23 (15 to 44), and +1.7 (0.6 to 2.8) years; for those aged 65 years or older, the metrics were 0.83 (95% CI: 0.73 to 0.94), 29 (17 to 83), and +0.9 (0.2 to 1.6) years, which provided evidence of a greater potential life extension in younger patients. Similar observations were found for lower risk patients. ConclusionsRMST event-free (and overall) survival estimates provided a complementary means of evaluating the effect of therapy in relation to age and risk. They also provided a clinically useful metric that should be routinely reported and used to explain the potential long-term benefits of a given treatment, especially to younger and less symptomatic patients.

Pulmonary hypertension due to left heart disease: diagnostic value of pulmonary artery distensibility.

To evaluate how pulmonary artery (PA) distensibility performs in detecting pulmonary hypertension due to left heart disease (PH-LHD) in comparison with parameters from ungated computed tomography (CT) and echocardiography. One hundred patients (79 men, mean age = 63 ± 17years) with either severe heart failure with reduced ejection fraction (HFrEF), aortic stenosis, or primary mitral regurgitation prospectively underwent right heart catheterization, ungated CT, ECG-gated CT, and echocardiography. During the ECG-gated CT, the right PA distensibility was calculated. In ungated CT, dPA, dPA/AA, the ratio of dPA to the diameter of the vertebra, segmental PA diameter, segmental PA-to-bronchus ratio, and the main PA volume were measured; the egg-and-banana sign was recorded. During echocardiography, the tricuspid regurgitation (TR) gradient was measured. The areas under the ROC curves (AUC) of these signs were computed and compared with DeLong test. Correlation between PA distensibility and PA pressure (PAP) was investigated through Pearson's coefficient. PA distensibility was lower in patients with PH than in those without PH (11.4 vs. 21.2%, p < 0.001) and correlated negatively with mean PAP (r = - 0.72, p < 0.001). Age, PA size, and mean PAP were independent predictors of PA distensibility. PA distensibility < 18% detected PH-LHD with 96% sensitivity and 73% specificity; its AUC was 0.92, larger than that of any other sign at ungated CT and TR gradient (AUC ranging from 0.54 to 0.83, DeLong: p ranging from 0.020 to < 0.001). PA distensibility on an ECG-gated CT can detect PH-LHD better than the parameters reflecting PA dilatation in ungated CT or TR gradient in the echocardiography of patients with severe HFrEF, aortic stenosis, or mitral regurgitation. • In left heart disease, pulmonary artery distensibility is lower in patients with PH than in those without pulmonary hypertension (11.4 vs. 21.2%, p < 0.001). • In left heart disease, pulmonary artery distensibility detects pulmonary hypertension with an area under the receiver operating curve of 0.92. • In left heart disease, the area under the receiver operating curve of pulmonary artery distensibility for detecting pulmonary hypertension is larger than that of all other signs at ungated CT (p from 0.019 to < 0.001) and tricuspid regurgitation gradient at echocardiography (p = 0.020).

Quantitative Metabolomics Reveals Heart Failure With Midrange Ejection Fraction as a Distinct Phenotype of Heart Failure

BackgroundHeart failure with midrange ejection fraction (HFmrEF) has been recently acknowledged as a separate phenotype, but metabolomics evaluation of this subtype remains largely unexamined. MethodsA quantitative metabolomics study on amino acids and acylcarnitines was performed to characterize different states of heart failure (HF) in 628 participants. Both multivariate orthogonal partial least squares- discriminant analysis and univariate Mann-Whitney U test were used to explore reliable metabolic profiles associated with different HF states. The resulting metabolites were further refined to obtain diagnostic metabolite scores (DMSs) with the use of ordinal logistic regression. Lasso-penalized regression was applied to produce a survival-associated prognostic metabolite score (PMS). The Cox proportional hazards model, Kaplan-Meier curves, and time-dependent receiver operating characteristics were used for a comprehensive assessment of prognostic value using PMS versus traditional clinical biomarkers. ResultsThe optimized models identified a panel of 15 differential metabolites that were shared across different HF states, whereas some metabolites were associated with a specific state. PMS consisting of 9 metabolites demonstrated an appreciably better prognostic value (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.25-2.1) vs the natural logarithm of N-terminal pro–B-type natriuretic peptide (Ln[NT-proBNP]; HR 1.23, 95% CI 0.94-1.61; P < 0.001). The overall area under the receiver operating characteristic curve value of PMS was superior to that of Ln(NT-proBNP) in risk prediction for patients with HFmrEF and HF with reduced ejection fraction (HFrEF) subtypes (P < 0.001). ConclusionsTargeted metabolomics has provided a novel understanding of the molecular mechanism underlying HF. Both DMS and PMS clearly demonstrated HFmrEF as a distinct phenotype between a mild HF with preserved ejection fraction state and a severe HFrEF state. PMS exhibited superior prognostic value than Ln(NT-proBNP). Further investigation is needed with independent large-scale validation.

Diaphragm weakness and proteomics (global and redox) modifications in heart failure with reduced ejection fraction in rats

Inspiratory dysfunction occurs in patients with heart failure with reduced ejection fraction (HFrEF) in a manner that depends on disease severity and by mechanisms that are not fully understood. In the current study, we tested whether HFrEF effects on diaphragm (inspiratory muscle) depend on disease severity and examined putative mechanisms for diaphragm abnormalities via global and redox proteomics. We allocated male rats into Sham, moderate (mHFrEF), or severe HFrEF (sHFrEF) induced by myocardial infarction and examined the diaphragm muscle. Both mHFrEF and sHFrEF caused atrophy in type IIa and IIb/x fibers. Maximal and twitch specific forces (N/cm2) were decreased by 19 ± 10% and 28 ± 13%, respectively, in sHFrEF (p < .05), but not in mHFrEF. Global proteomics revealed upregulation of sarcomeric proteins and downregulation of ribosomal and glucose metabolism proteins in sHFrEF. Redox proteomics showed that sHFrEF increased reversibly oxidized cysteine in cytoskeletal and thin filament proteins and methionine in skeletal muscle α-actin (range 0.5 to 3.3-fold; p < .05). In conclusion, fiber atrophy plus contractile dysfunction caused diaphragm weakness in HFrEF. Decreased ribosomal proteins and heighted reversible oxidation of protein thiols are candidate mechanisms for atrophy or anabolic resistance as well as loss of specific force in sHFrEF.

166 Single Centre Experience with Heart Function Clinic and Heart Failure Admissions

Heart failure admissions contribute significantly to health care expenditure. Multidisciplinary heart failure clinic (HFC) may reduce readmission rate and mortality. We conducted a retrospective audit of heart failure admissions under the Cardiology Service in 2018. 178 of 198 admitted patients were analysed. Baseline characteristics: male 67.4%, average age 72.6y. Co-morbidities: ischaemic heart disease (47.4%), atrial fibrillation (50.9%), diabetes (37.1%), hypertension (64.6%), lung pathology (27.4%) and chronic kidney disease (43.4%). Heart failure with preserved ejection fraction (HFpEF) accounted for 30.9% and heart failure with reduced ejection fraction (HFrEF) accounted for 60.5% of patients. HFpEF patients were older than HFrEF patients (76.3 vs 70.5y, p=0.01). HFpEF were less likely to attend HFC (38.9% of all HFpEF patients), compared with 50.9% of all HFrEF patients attending HFC. Length of stay (LOS) for index admission was similar in both groups (4.1 vs 4.3 days in HFpEF and HFrEF respectively). There was no difference in median total admissions over 12 months between the groups. Patients attending HFC had numerically increased median LOS during index admission (6.0 vs 4.9 days, p=0.07). There was a trend towards increased severity of HFrEF patients attending HFC. The burden of HFpEF on inpatient services are similar to those of HFrEF, with no difference in median LOS or admission rate. Despite this, they are under-represented in HFC. Increased LOS in patients attending HFC likely represents referral bias of unwell patients with severe HFrEF.

Research into the Effect of Sodium-Glucose Linked Transporter 2 Inhibition on Left Ventricular Remodeling in Patients with Heart Failure and Diabetes Mellitus

Introduction: DM and heart failure (HF) are lethal, with limited diabetic therapy options. Sodium-glucose linked transporter 2 (SGLT2) inhibitors have been reported to have CV benefits in at risk DM patients. We are the first to study the CV effects of SGLT2 inhibition in patients with DM and HF. Methods: In this randomized double-blind placebo controlled trial, 56 patients (mean age: 67.1 years, males: 66%) with DM and echocardiographically confirmed HF with reduced ejection fraction (HFrEF) on regular diuretic therapy were assigned to dapagliflozin 10mg OD or placebo for one year. Primary endpoint was the difference in left ventricular (LV) volumes between both groups using cardiac MRI. Secondary endpoints include LV mass, LV ejection fraction (EF), weight, BP and diuretic use. Outcomes were analysed using linear regression controlling for baseline values, age, sex and renal function. Results: There was no difference between dapagliflozin and placebo in the primary endpoints of LV end diastolic volume (LVEDV) or LV end systolic volume (LVESV); +4.71mls; 95% CI: -17.to 26.50 and +1.52mls; 95% CI: -15.68 to 18.72 respectively. However, when an interaction term for starting LVEF was added to the model, dapagliflozin significantly lowered LVEDV, LVESV and LV mass in those with starting LVEF ≥ 45%; -15.59mls; p=0.019, -15.20mls; p=0.016 and -4.87gm/m2; p=0.026. Patients on dapagliflozin had weight reduction; -1.90kg; 95% CI: -3.83 to +0.04; p=0.054, lower diastolic BP; -6.34mmHg; 95% CI: -11.35 to -1.32; p=0.014 and higher hemoglobin; +1.23 g/dl; 95% CI: 0.65 to 1.82; p&amp;lt;0.001. They were also more likely to stop or reduce loop diuretics; 50.0% vs. 8.7%; p=0.005. Conclusions: Our data show dapagliflozin treatment resulted in weight and blood pressure reduction among patients with DM and HFrEF. There was evidence to suggest that dapagliflozin may cause LV reverse remodelling in DM patients with mild, but not with more severe HFrEF. Disclosure J.S.S. Singh: None.I. Mordi: None.M. Mohan: None.S.J. Gandy: None. E. Pearson: Speaker's Bureau; Self; Eli Lilly and Company.J.G. Houston: None. A.D. Struthers: Research Support; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca.C.C. Lang: None.

Multidimensional contractile reserve predicts adverse outcome in patients with severe systolic heart failure: a 4-year follow-up study.

Left ventricular contractile reserve is a prognostic indicator for adverse outcome in patients with severe chronic heart failure with reduced ejection fraction (HFrEF). We investigated the dobutamine-induced changes of LV multidimensional deformation and their predictive value for cardiac mortality of patients with severe chronic HFrEF. In this prospective study, out of 130 patients with severe HFrEF who underwent a low-dose dobutamine stress echocardiography (LDSE) study using speckle tracking imaging, 100 patients were followed up for the occurrence of cardiac death over a period of 4 years. Compared with survivors, non-survivors (n = 32) had lower radial strain (RS) and strain rate (RSR) (10.7 ± 5.9 vs. 20.1 ± 8% and 0.5 ± 0.2 vs. 0.8 ± 0.3 L/s, P < 0.001), a smaller increase of global longitudinal strain (GLS) and strain rate after LDSE (0.9 ± 1.5 vs. -3.3 ± 3.5% and -0.1 ± 0.1 vs. -0.3 ± 0.3 L/s, P < 0.001), and a lack of change in the circumferential and radial deformation. The dobutamine-induced changes of all speckle tracking indices predicted cardiac mortality, while, among resting echocardiographic parameters, only RS and RSR predicted survival, after adjusting for age, sex, cardiomyopathy aetiology, NYHA class, AF, BNP levels, resting LVED, and LV outflow tract velocity-time integral, and their respective changes produced by dobutamine (P < 0.05). The dobutamine-induced change of GLS and resting RS were the best additive predictors of mortality with a net reclassification improvement of 0.518 (P = 0.022) CONCLUSION: In severe chronic HFrEF, resting RS and the dobutamine-induced change of GLS are independent predictors of cardiac mortality.

Blood leukocytes in heart failure with preserved ejection fraction: Impact on prognosis

Heart failure (HF) with preserved ejection fraction (HFpEF) is an emerging problem of cardiovascular medicine with increasing prevalence and poor prognosis [1,2]. The pathophysiological mechanisms of HFpEF are still poorly understood. Leukocytes play important role in the pathogenesis and prognosis of HF with reduced ejection fraction (HFrEF) via their contribution to inflammation, extracellular matrix remodelling, and reparatory processes [3]. Relative lymphopenia is a strong predictor of mortality in severe HFrEF [4,5]. In contrast, neutrophils are often increased in HFrEF and pose an increased risk of all-cause and cardiovascular mortality [6]. However, only scarce data are available on the impact of leukocytes on pathophysiology and outcome in HFpEF. In this study we aimed to compare levels of neutrophiles, lymphocytes and monocytes between patients with HFrEF and HFpEF and to establish their impact on the mortality in HFpEF. The total number of 1019 HF patients referred the Cardiology Clinic of the Grodno Regional Clinical Hospital in 2008–2009 with either HFpEF (n=856, age 55[49–64], 81% males) or HFrEF (n=163, age 58[51–65], 56% males) were included into the study. The diagnosis of HFrEF or HFpEF was established according to the current ESC guidelines [7]. Patients with life expectancy b1 year due to noncardiac courses (e.g., cancer) and those with terminal HF (NYHA class IV) were not included. All subjects underwent transthoracic echocardiography with LVEF measured using the modified Simpson's biplane method and diastolic function assessed by evaluating E/A ratio. The leucocytes were measured using an automatic haematocytometer (Micros-60 Horiba, ABX Diagnostics, France). The patients were followed for at least 1 year with median (interquartile range) follow-up duration of 17[14–20]months with the end-point of any-cause death registered. The study was approved by the Institutional Research Board of the Grodno State Medical University. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [8]. Most patients had mild HF (NYHA I–II class in 98% of HFpEF, 82% of HFrEF) predominantly of ischemic aetiology (74% of HFpEF, 73% of HFrEF). Patients with HFrEF had lower body mass index (p=0.017), and proportion of patients with history of hypertension (pb0.001), higher proportions of males (pb0.001), and subjects with history of previous myocardial infarction (p=0.002). PatientswithHFpEF as comparedwithHFrEF had significantly lower neutrophil count (4140[3498–5293] vs. 3933[3247–4760] per μl, p=0.004) and percentage (63[58–68]% vs. 65[59–69]%, p=0.018) and higher lymphocyte percentage (30[26–34]% vs. 29[24–33], p=0.004). On regression analysis, significant clinical predictors of reduced LVEF in the whole study population were advanced age, male sex, history of hypertension and atrial fibrillation (pb0.05). Among leukocytes, high neutrophil count and percentage and low lymphocyte percentage were associated with reduced LVEF and remained so after adjustment for the clinical predictors above (pb0.05). During the follow-up period, 41 deaths (4.02%) occurred (28 in HFpEF and 13 in HFrEF). Using logistic regression analysis, a history of hypertension was the only significant clinical predictor of death in HFpEF. Among leukocytes, high monocyte count was predictive of death in HFpEF before (p=0.01) and after (p=0.012) adjustment for age, LVEF, and hypertension (p=0.012) (Table 1). In HFpEF 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.12.049